The central theme of this Program Project competitive renewal proposal is the fundamental development of functional magnetic resonance imaging (fMRI) into a quantitative basis of mental health. Project I proposes a testable model of fMRI contrast expressed in terms of cerebral blood flow, blood volume and metabolism. It uses a rat fMRI model as well as human subjects to probe issues of fMRI spatial resolution and temporal response and of spontaneous fluctuations in these physiological parameters. Project II addresses polymodal sensory and attentional interactions. It seeks to determine rules governing polymodal interactions using visual and auditory motion processing paradigms as an essential step in understanding sensory and attentional deficits caused by brain pathology. Project II is designed to understand how temporal information is represented in the brain. Using pharmacological probes of normal subjects and studies of patients with basal ganglia disease, this project will test the hypothesis that a unified neural system mediates both perceptual and motor timing. Project IV is built on the experimental observation that "negative" fMRI responses are most frequently seen in brain areas that have also been implicated in semantic processing. It tests the hypothesis that non-semantic tasks produce decreases in neural activity in regions normally engaged in semantic processing. If true, novel research approaches to several neuropsychiatric diseases become available. Core A, Administration, in addition to normal activities, places emphasis on coordinating development of local brain gradient and RF coil technology. Core B focuses on fMRI technology development including interactive real time fMRI at 1/5 and 3 Tesla and extension of the integrated software system AFNI developed in the previous funding period. Core C provides stimulus delivery and subject monitoring capabilities and will continue to refine the Mock scanner for acquiring behavioral and psychophysical data in a simulated MRI environment. These closely integrated initiatives seek to extend fMRI beyond simple mapping into a technique for probing the integration of diverse brain systems in order to make further progress towards the long-term goal of application of fMRI to neuropsychiatric disease and mental health.